Method for plasma charging a probe

ABSTRACT

A method for electrically charging a probe by plasma technology for use in pipetting compounds in small volumes includes the steps of placing the probe to be charged in a plasma chamber, creating a vacuum within the plasma chamber and then introducing a stable gas into the plasma chamber, applying electromagnetic energy to the plasma chamber, thereby molecularly disassociating the gas, thus creating charged ions, free electrons, and free radicals, charging the probe by the free radicals attaching to the probe, venting the plasma chamber to back to atmospheric pressure; and removing the charged probe from the plasma chamber, whereby the charged probe can pipette compounds in small volumes. The method is applicable to pipetting both liquid and solid compounds. In another embodiment, the plasma generation is at atmospheric pressure without a containment chamber and the surface charging effect is used for surfaces of both the fluid dispensing device and the fluid containing device. The component surfaces of the fluid dispensing or fluid containing device are placed in proximity to the plasma generation device within the area of plasma generation, electromagnetic energy is applied to the existing atmospheric gas or to the existing atmospheric gas with other gases added, thereby molecularly disassociating the gas, thus creating charged ions, free electrons, and free radicals, charging the surfaces of the fluid dispensing or fluid containing device and then removing the fluid dispensing or fluid containing device from the area of plasma generation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application derives priority from co-pending U.S. Ser. No.60/176,201, filed Jan. 14, 2000, and is a continuation-in-part of U.S.patent application Ser. No. 09/765,733, filed Jan. 12, 2001 andPCT/US01/01262 filed Jan. 12, 2001.

FIELD OF THE INVENTION

The present invention relates to a method for use of plasma to apply acontrolled charge to a surface.

BACKGROUND OF THE INVENTION

Within the disciplines of the clinical, industrial and life sciencelaboratory, scientists perform methods and protocols with extremelysmall quantities of fluids. These fluids consist of many categories andtypes with various physical properties Many times volumes are workedwith that are between a drop (about 25 microliters) and a fewnanoliters. There are a number of standard methods employed to transferliquid compounds from a source by aspirating the liquid from such fluidholding device into the fluid dispensing device having a probe, cannula,pin tool or other similar component or plurality of components whichmove, manually or robotically, and then dispensing, from the same probeor plurality of probes, into another fluid holding device.

Four common techniques are (1) a scheme using a probe or cannula, thatmay or may not be coated with a layer of material or special coating,which is attached directly or by a tube to a pumping device, (2) ascheme using a disposable pipet instead of the probe/cannula butotherwise similar, (3) a scheme using a spray head with one or aplurality of openings and pumping system that physically propelsmultiple precisely metered microdroplets, and (4) a scheme using metalshafts with precisely machined hollowed out spaces at their ends thathold the fluid by surface tension (commonly referred to as a “pintool”).

As routine a process as fluid transfer is in the laboratory, technicalchallenges to achieve suitable levels of precision and accuracy remainAs the volume decreases, it becomes progressively more technicallychallenging to aspirate and dispense these very small quantities offluids due to the various effects of interaction between the dispensingdevice and the fluid. Droplet formation, as the fluid is dispensed, is achange in the shape of the fluid. The droplet experiences changes ininternal forces during the process (eg, surface tension, viscosity, andpolarity) and in external forces due to interactions between the fluidand the surfaces of the probe, cannula, pin tool or other similarcomponent (e.g., superficial and interfacial energies). It is desirableto control and be able to use these forces to improve the process. Theuse of low temperature atmospheric plasma in such a way so as to place acharge on the probe, cannula, pin tool or other similar component, inorder to control properties of the surface of the probe, cannula, pintool or other similar component in order to attract or repel the fluidaccomplishes this desired objective. This control is achieved bymetering the deposition of charge by the plasma. The optimum conditionsfor fluid transfer can be reached taking into consideration theapplication, fluid characteristics, the affect of any compound dissolvedin the liquid, the affect of any particles or other physical matter inthe liquid and the type of probe or delivery mechanism used.

The charge from the plasma on the surfaces of the probe, cannula, pintool or other similar component will alter forces effecting dropletformation, the force required to release the droplet from the probe,cannula, pin tool or other similar component the surface tensioninteraction between the liquid and the probe, cannula, pin tool or othersimilar component, and help suppress the formation of microdroplets(parts of the fluid being transferred that can break off) duringdispensing. Some fluid dispensing devices allow the plasma to be pulledinto the internal spaces of the probe, cannula or other similarcomponent. The plasma generated surface effects on the fluid inside willhave similar action as on the outside surfaces. Exposing the internalsurfaces of the probe, cannula or other similar component addsadditional control to the total affect of the plasma charge on the fluidhandling process.

The same surface effect of the plasma charge on the surfaces of thedispensing device can be applied to the surfaces of the fluid containingdevice into or onto which the fluid is dispensed. The controlled chargecan improve the flow of the small fluid droplets down the side wall of atube or microplate well and will affect the shape of the fluid dropletformation at the bottom of a tube, microplate well or fluid processingsurface. As volumes being transferred decrease, the affect of the plasmacharge on the surface becomes more important. On fluid processingsurfaces (surfaces onto which droplets are transferred but without aside wall defining a tube or well), the shape of the droplets on thesurface determines the diameter and depth of the fluid at a defineddroplet volume. The charge on the surface of the plate can alter andthereby control the forces of interaction between the droplet and theplate and, as a result, control these parameters.

Plasma technology is known in the art and is presently used inconnection with a wide variety of applications. The most common uses ofplasma are based on technologies that rely on the generation of plasmain a low pressure environment.

To sterilize medical devices, a technique known as glow discharge isoften used, in which the items are sterilized in air, as opposed to agas-filled evacuated chamber. For example, U.S. Pat. No. 5,633,424relates to a method of sterilizing items using water vapor-based plasma.The items to be sterilized are placed in a chamber, which is thenevacuated. Water vapor is introduced into the chamber and is allowed touniformly disperse throughout the chamber. Electromagnetic radiationenergy is then applied to the chamber, fractionating the water moleculesinto reactive radicals. These radicals then combine with themicroorganisms on the items, effectively vaporizing the microorganisms.The by-product gases are exhausted from the chamber, and thenow-sterilized items can be removed from the chamber.

U.S. Pat. No. 5,700,327 recites a method for removing organic compoundsfrom hollow containers, thereby cleaning the containers. The containeris placed into a vacuum chamber, and an oxidizing gas is introduced intothe chamber. An electric field is then applied to the chamber,converting the oxidizing gas into low temperature plasma, which thenoxidizes substantially all of the organic compounds within thecontainer.

U.S. Pat. No. 6,059,935 discloses two methods and correspondingelectrode designs for the generation of a plasma, for example, at orabout one atmosphere. Using the disclosed methods, various webs, filmsand three-dimensional objects are beneficially treated in a reducedamount of time. A first method utilizes a repetitive, asymmetric voltagepulse to generate a plasma discharge between two electrodes. Anasymmetric voltage pulse is used to generate a discharge in which asubstrate can be exposed predominately to either positive or negativeplasma species depending on the voltage polarity used. A second methoduses the gap capacitance of an electrode pair and an external inductorin shunt to form a resonant IC circuit. The circuit is driven by a highpower radio frequency source operating at 1 to 30 MHz to generate auniform discharge between the electrode pair. Both methods havetemperature controlled discharge surfaces with supply gas temperature,humidity and flow rate control. The gas flow is typically sufficient tocause a turbulent flow field in the discharge region where materials aretreated. Electrode pairs implement these methods and include a metalfaced electrode and a dielectric covered electrode, one or both of whichhave a series of holes extending through the electrode face for supplygas flow. The second of the above-described methods will also operatewith paired, metal faced electrodes, but under more restricted operatingconditions.

U.S. Pat. No. 6,132,813 discloses a method for modifying a substratesurface, including the step of applying a high density plasma to thesubstrate surface in-the presence of a hydrofluorocarbon gas and acarrier gas to form an antiwetting layer on the substrate surface.Optionally, the method includes a cleaning step of contacting the slidersurface with a carrier gas for a period of time effective to clean thesurface.

U.S. Pat. No. 6,105,589 is directed to an improved method and apparatusare provided for cleaning the specimen and interior specimen chamber ofelectron microscopes, and similar electron beam instruments. Theapparatus consists of a glow-discharge, oxygen-radical generator placedon a specimen chamber port with an excitation source to create alow-power glow-discharge plasma inside the generator. Air or otheroxygen and nitrogen mixture is admitted to the generator at a pressurebetween 0.3 Torr and 5 Torr. The low power glow discharge is used todisassociate oxygen preferentially over nitrogen to create the oxygenradicals. The oxygen radicals then disperse by convection throughout thechamber to clean hydrocarbons from the surfaces of the chamber, stageand specimen by oxidation to CO and H20 gases.

A number of patents have been issued for plasma generation atatmospheric pressure. Current research with these basic methods hasallowed the development of a number of plasma techniques formerly onlydone at low pressure to be performed at atmospheric pressure.Atmospheric plasma generation has its own set of technical advantagesand disadvantages.

U.S. Pat. No. 5,977,715 discloses an atmospheric pressure glow dischargeplasma source without the use of an arc. The plasma chamber is capableof producing stable plasma in Ar, He and O2 mixtures using a low voltageRF power supply.

U.S. Pat. Nos. 5,872,426 and 6,005,349 (a division of application Ser.No. 08/820,013, filed Mar. 18, 1997, now U.S. Pat. No. 5,872,426) andU.S. Pat. No. 6,147,452 (a continuation-in-part application Ser. No.08/820,013, filed Mar. 18, 1997, now U.S. Pat. No. 5,872,426) disclose anumber of methods and apparatus for stabilizing glow plasma dischargesby suppressing the transition from glow-to-arc by including a perforateddielectric plate with characteristics detailed in the patent. Thepatents detail embodiments with a wide range of electric fieldsincluding DC and RE fields of varying strength and an AC glow dischargedevice in which the frequency of the AC source is adjusted to be matchedto the characteristics of the apertured dielectric. In this embodimentjets come out of the apertures at the proper frequency.

In U.S. Pat. No. 6,262,523 the patent discloses the device to generate alarge area atmospheric-pressure plasma jet that can be operated nearroom temperature. The jet can extend up to 8 inches beyond the open endof the electrodes.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a diagram of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 outlines the steps of the method of the present invention. First,a probe or other type of fluid handling device, preferably coated with amaterial optimized to the fluid characteristics of the application, suchas TEFLON-coated but applying to probes with any coating, is placed intoeither a plasma chamber and the chamber is sealed or is placed inproximity to a low temperature, atmospheric plasma source within thearea that plasma will be generated.

In the instance of using a plasma chamber, a vacuum is crated in thesealed plasma chamber, and oxygen gas, along with an argon carrier gas,is introduced into the chamber and dissipates throughout the chamber.Sufficient electromagnetic energy is added to the chamber to ionize theoxygen gas within the carrier gas mixture, creating mainly 0 ions, freeelectrons, and free radicals. Because the probe has very little organicmaterial on the surfaces when it is placed in the plasma chamber, whatorganic material that is present is quickly removed and the ions andfree radicals have no other substance to attach to, and cling to theprobe, thereby imparting a charge to the probe. The vacuum chamber isthen vented, returning it to atmospheric pressure, and the now-chargedprobe is removed from the chamber.

In the instance of using a low temperature, atmospheric plasma, themethod is similar except no vacuum or chamber is required and venting isunnecessary. In either instance, the probe is charged by the plasma in acontrolled and precise manner.

This method is performed by a machine that does not require humancontact with the probe, which could dissipate the charge and possibly“contaminate” the probe. Under these conditions, the method is performedsimilar to a “tip wash” as is commonly performed. This method can beused as a replacement for a “tip wash”, as any organic material on theprobe will be ionized, oxidized and/or vaporized by the plasma as theprobe is charged by the plasma.

After the probe has been plasma-charged according to the method, it canbe used to pipette liquid compounds. The compounds being pipetted withthe probe can be quite variable in consistency and physical properties.The major variables affecting the consistency of a liquid compoundtransfer are surface charge characteristics (hydrophilic tohydrophobic), viscosity, polarity (the electric charge of the solventand solute), pH, ionic strength, and vapor pressure.

By using the plasma-charging method, the surface characteristics of aprobe can be modified to optimize pipetting characteristics of differenttypes of compounds used and otherwise reduce the interaction of thefluid and surface material. The surface characteristics can be “tuned”to the optimum requirements for a compound. By modifying the surfacecharacteristics this manner, the pipetting system can work moreoptimally over a broader range of compounds and solvents, such as thoseused in drug discovery and other life science applications. This controlis critical when working with small volumes. At low volumes, mostnoticeably at single digit microliter quantities or less, compoundcharacteristics will cause a liquid to cling to the surface it isattached to and remain attached to the column of fluid from which it isbeing metered, thus making the accurate and reproducible metering ofthese small volumes difficult. Applying a charge to the probe canovercome a liquid's tendency to cling to other surfaces and reduce anumber of other phenomena that degrade the precision and accuracy of thefluid handling process.

It will be understood that the embodiment described herein is merelyexemplary and that a person skilled in the art may make many variationsand modifications without departing from the spirit and scope of thepresent invention. For example, the method can also be applied tocharging a probe for use in connection with solid (i.e., dry) compounds.All such variations and modifications are intended to be included withinthe scope of the invention as defined in the appended claims.

1. A method for electrically charging a probe, cannula, pin tool orother similar component or plurality of such components made of anymaterial of a fluid dispensing device used to pipet small volumes offluids by plasma technology comprising the following steps: placing suchprobe, cannula, pin tool or other similar component or plurality of suchcomponents to be charged in a space that plasma is generated by a plasmagenerating device; applying electromagnetic energy to the plasmagenerating device, thereby molecularly disassociating the gas, thuscreating charged ions, free electrons, and free radicals, and chargingthe surface by the charged ions and free radicals attaching to theprobe, cannula, pin tool or other similar component or plurality of suchcomponents, removing the charged probe, cannula, pin tool or othersimilar component or plurality of such components from the area ofplasma generation, whereby the charged probe, cannula, pin tool or othersimilar component or plurality of such components can pipette compoundsin small volumes.
 2. A method for electrically charging a probe,cannula, pin tool or other similar component or plurality of suchcomponents made of any material of a fluid dispensing device used topipet small volumes of fluids by plasma technology comprising thefollowing steps: placing such probe, cannula, pin tool or other similarcomponent or plurality of such components to be charged within in aspace that plasma is generated by a plasma generating device; using theplasma generating device to introduce a gas mixture of oxygen and acarrier gas into the plasma, and applying electromagnetic energy to thegas mixture, thereby causing a breakdown of the Oxygen (O₂) moleculesinto O ions, free electrons, and free radicals; (i.e., the plasma),thereby causing the ions and free radicals to attack and attach to theprobe, cannula, pin tool or other similar component or plurality of suchcomponents, thereby imparting a charge to the surface removing thecharged probe, cannula, pin tool or other similar component or pluralityof such components from the area of plasma generation, whereby thecharged probe, cannula, pin tool or other similar component or pluralityof such components can pipette compounds in small volumes.
 3. The methodof claim 2 wherein the carrier gas is argon.
 4. A method forelectrically charging a probe, cannula, pin tool or other similarcomponent or plurality of such components made of any material of afluid dispensing device and coated with one or more additional materialsor treatments used to pipet small volumes of fluids by plasma technologycomprising the following steps: placing such coated probe, cannula, pintool or other similar component or plurality of such components with aphysical coating or permanent surface treatment to be charged in a spacethat plasma is generated by a plasma generating device, applyingelectromagnetic energy to the plasma generating device, therebymolecularly disassociating the gas, thus creating charged ions, freeelectrons, and free, radicals, and charging the surface by the chargedions and free radicals attaching to the probe, cannula, pin tool orother similar component or plurality of such components, removing thecharged probe, cannula, pin tool or other similar component or pluralityof such components from the area of plasma generation, whereby thecharged probe, cannula, pin tool or other similar component or pluralityof such components can pipette compounds in small volumes.
 5. Themethods of claims 1 for electrically charging a probe, cannula, pin toolor other similar component or plurality of such components made of anymaterial of a fluid dispensing device used to pipet small volumes offluids by plasma technology comprising the following steps: placing suchprobe, cannula, pin tool or other similar component or plurality of suchcomponents to be charged in a space that plasma is generated by a plasmagenerating device, applying electromagnetic energy to the plasmagenerating device, thereby molecularly disassociating the gas, thuscreating charged ions, free electrons, and free radicals, and chargingthe probe by the charged ions and free radicals attaching to the probe,cannula, pin tool or other similar component or plurality of suchcomponents, using the fluid dispensing device to create a backpressureor vacuum within the probe, cannula or other similar component orplurality of such components and pulling the plasma into the interiorspace of the probe, cannula or other similar component or plurality ofsuch components using the fluid handling device to create a positivepressure within the probe, cannula or other similar component orplurality of such components to expel the plasma from the interior spaceof the probe, cannula or other similar component or plurality of suchcomponents. repeating the prior two steps, as desired. removing thecharged component from the area of plasma generation, whereby thecharged probe, cannula or other similar component or plurality of suchcomponents can pipette compounds in small volumes.
 6. A method forelectrically charging the surfaces of a fluid containing device, suchas, but not limited to, a tube or microplate made of any material, withone or a plurality of containment wells or fluid processing surface,made of any material including but not limited to plastic, composite,glass or silicon, by plasma technology for use in manipulating smallvolumes of fluids comprising the following steps: placing suchcontainer, having a tube like structure or wells for containing suchfluid or a surface to place drops of fluids into a position so as to beexposed appropriately to the plasma, applying electromagnetic energy tothe plasma generating device, thereby molecularly disassociating thegas, thus creating charged ions, free electrons, and free radicals, andcharging the probe by the charged ions and free radicals attaching tothe surfaces to be treated; moving or leaving in place the containingdevice or surface for the dispensing of small volumes of fluid, orremoving or leaving in place the containing device or surface withoutfurther processing.
 7. The method in claim 6 using a gas mixture ofoxygen and a carrier gas.
 8. The method in claim 6 using with thecarrier gas argon.
 9. The method in claim 6 with the plasma charge beingapplied on a one or more coating materials or treatments on thecontainment device or surface.